Research on a number of problems of evolutionary genetics will be carried out, using a combination of genetic, molecular and theoretical approaches. This will enhance our understanding of evolutionary processes and the causes of natural variation. Such an understanding is critical for the proper use of DNA sequence data, and for the study of human genetic disorders, as well as for its intrinsic interest. The question of the genetic mechanism involved in the evolution of sex chromosomes will be studied by (i) initiating the genetic and molecular analysis of the Y chromosome of the white campion, Silene latifolia (ii) examining the neo-Y chromosome of Drosophila americana for evidence that it has been invaded by transposable elements. Evidence on the rate of evolution of X-linked genes compared with autosomes will be sought using DNA sequencing of clone Drosophila gene that are present on the X chromosomes of some species, but which are autosomal in others. A faster rate of adaptive evolution of X-linked loci might play a role in shaping the nature of the genetic control of reproductive isolation. This control will be studied in two separate projects on Drosophila. One of these will be concerned with the refinement of the molecular genetic analysis of hybrid male sterility, including the aim of cloning an X- chromosome locus that has been identified in crosses between D. simulans and D. mauritiana. The other will be concerned with the classical genetic and biochemical analysis of mating discrimination among Drosophila species. The constraints imposed by the breeding system on the amount and nature of natural variation will be studied by comparing DNA sequence variation in related inbreeding and outbreeding species of Brassicaceous plants. Theoretical models relevant to interpreting the results of this study will also be developed. Finally, the evolutionary genetics of a cytoplasmic endosymbiont, Wolbachia, will be studied, by a combination of theoretical and experimental approaches.